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1.
Expert Rev Anticancer Ther ; 24(7): 613-622, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761169

RESUMO

INTRODUCTION: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database. METHODS: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database. RESULTS: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation. CONCLUSION: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months. REGISTRATION: PROSPERO (CRD42022385274).


Assuntos
Doenças Hematológicas , Neoplasias , Farmacovigilância , Inibidores de Poli(ADP-Ribose) Polimerases , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Neoplasias/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Bases de Dados Factuais , Ftalazinas , Piperazinas
2.
World J Gastrointest Surg ; 16(1): 196-204, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38328336

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) combined with microwave ablation (MWA) is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis. However, it may cause severe postoperative pain and inflammatory responses. The paravertebral block (PVB) is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions. AIM: To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis. METHODS: Sixty patients were randomly divided into PVB and control groups. The PVB group received ultrasound-guided PVB with 0.375% ropivacaine preoperatively, whereas the control group received intravenous analgesia with sufentanil. The primary outcome was the visual analog scale (VAS) score for pain at 6 h, 12 h, 24 h, and 48 h after the procedure. Secondary outcomes were the dose of sufentanil used, incidence of adverse events, and levels of inflammatory markers (white blood cell count, neutrophil percentage, C-reactive protein, and procalcitonin) before and after the procedure. RESULTS: The PVB group had significantly lower VAS scores at 6 h, 12 h, 24 h, and 48 h after the procedure compared with the control group (P < 0.05). The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea, vomiting, and respiratory depression than did the control group (P < 0.05). Compared with the control group, the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure (P < 0.05). CONCLUSION: PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

3.
Food Chem Toxicol ; 178: 113874, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37286030

RESUMO

The type B trichothecenes pollute food crops and have been associated to alimentary toxicosis resulted in emetic reaction in human and animal. This group of mycotoxins consists deoxynivalenol (DON) and four structurally related congeners: 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl deoxynivalenol (15-ADON), nivalenol (NIV) and 4-acetyl-nivalenol (fusarenon X, FX). While emesis induced by intraperitoneally dosed to DON in the mink has been related to plasma up-grading of 5-hydroxytryptamine (5-HT) and neurotransmitters peptide YY (PYY), the impact of oral dosing with DON or its four congeners on secretion of these chemical substances have not been established. The aim of this work was to contraste emetic influence to type B trichothecene mycotoxins by orally dosing and involve these influence to PYY and 5-HT. All five toxins attracted marked emetic reaction that are relevant to elevated PYY and 5-HT. The reduction in vomiting induced by the five toxins and PYY was due to blocking of the neuropeptide Y2 receptor. The inhibition of the induced vomiting response by 5-HT and all five toxins is regulated by the 5-HT3 receptor inhibitor granisetron. In a word, our results indicate that PYY and 5-HT take a key role in the emetic reaction evoked by type B trichothecenes.


Assuntos
Micotoxinas , Tricotecenos do Tipo B , Tricotecenos , Animais , Humanos , Serotonina , Eméticos/efeitos adversos , Peptídeo YY , Tricotecenos do Tipo B/efeitos adversos , Vômito/induzido quimicamente , Tricotecenos/toxicidade , Micotoxinas/efeitos adversos , Vison
4.
World J Clin Cases ; 11(11): 2535-2540, 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37123306

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS) has been associated with gout and type 2 diabetes mellitus (T2DM). However, due to insufficient clinical understanding of gout-related CTS and reliance on the diagnostic importance of elevated serum uric acid levels, such cases are prone to missed diagnosis, misdiagnosis, and delayed treatment. In addition, the effect of T2DM on gout - induced carpal tunnel syndrome has not been reported. CASE SUMMARY: Herein, we present an unusual case of CTS and motor dysfunction caused by miliary tophaceous gout and T2DM. The patient presented to the hand and foot clinic with paresthesia of the fingers of both hands, especially at night. The patient was diagnosed with type 2 diabetes a month ago. Ultrasonography revealed bilateral transverse carpal ligament thickening with median nerve compression during hospitalization. The patient was successfully treated with carpal tunnel decompression and tendon release. The postoperative pathological examination revealed typical gout nodules. This case suggests that the presence of T2DM could accelerate tophi formation and worsen CTS symptoms, although no definitive proof in this regard has been described previously. CONCLUSION: Tophi formation may most likely cause the co-occurrence of CTS and flexor dysfunction in gout and incipient diabetes patients.

5.
J Neuroimmunol ; 378: 578089, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37094438

RESUMO

OBJECTIVE: To systematically evaluate the risk factors of post-encephalitis epilepsy (PEE). METHODS: Systematic computerized searches of databases such as Cochrane Library, PubMed and EMBASE were performed. The meta-analysis of pooled odds ratios and 95% confidence intervals for PEE risk were calculated. RESULTS: Sixteen studies with 2504 patients were included for meta-analysis. The results showed that PEE was associated with coma, seizure, status epilepticus, cranial MRI abnormality, focal EEG abnormality, and positive herpes simplex virus (HSV) in cerebrospinal fluid (CSF). CONCLUSION: Coma, seizures or status epilepticus, abnormal MRI and focal EEG, and HSV in CSF were the risk factors of PEE.


Assuntos
Encefalite por Herpes Simples , Encefalite Viral , Encefalite , Epilepsia , Estado Epiléptico , Humanos , Coma/complicações , Epilepsia/diagnóstico por imagem , Epilepsia/epidemiologia , Epilepsia/etiologia , Encefalite Viral/complicações , Encefalite Viral/diagnóstico por imagem , Convulsões , Fatores de Risco , Estado Epiléptico/etiologia , Encefalite/complicações
6.
Cell Tissue Res ; 391(3): 419-423, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36705748

RESUMO

Stem cells possess the capability of self-renewal and multipotency, which endows them with great application potential in wound repair fields. Yet, several problems including immune concerns, ethical debates, and oncogenicity impede the broad and deep advance of stem cell-based products. Recently, owing to their abundant resources, excellent biocompatibility, and ease of being engineered, stem cell-derived exosomes were proved to be promising nanomedicine for curing chronic wounds. What is more, stem cell-derived exosomes are almost the mini record of their maternal cells, which even equipped them with the unique characteristics of stem cells. Chronic wound healing efficacy is dominated by several complicated factors, especially the excessive inflammation conditions and impaired vessels. Therefore, this review tries to concentrate on the current advances of stem cell-derived exosomes for reducing inflammation and promoting angiogenesis in chronic wound healing processes. Last but not least, the existing limitations and future perspectives of stem cell-derived exosomes for chronic wound treatment are also outlined.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Cicatrização , Células-Tronco , Inflamação
7.
ACS Biomater Sci Eng ; 9(2): 531-541, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36607315

RESUMO

A skin wound represents a rupture caused by external damage or the existence of underlying pathological conditions. Sometimes, skin wound healing processes may place a heavy burden on patients, families, and society. Wound healing processes mainly consist of several continuous, dynamic, but overlapping stages, namely, the coagulation stage, inflammation stage, proliferation stage, and remodeling stage. Bacterial infection, excessive inflammation, impaired angiogenesis, and scar formation constitute the four significant factors impeding the recovery efficacy of skin wounds. This encourages scientists to develop multifunctional nanomedicines to meet challenging needs. As we know, mesenchymal stem cells (MSCs) have been widely explored for wound repair owing to their unique capability for self-renewal and multipotency. However, problems including immune concerns and legal restrictions should be properly resolved before MSC-based therapeutics are safely and widely used in clinics. Besides, maintaining the high viability/proliferation capability of MSCs during administration processes and therapy procedures is also one of the biggest technical bottlenecks. Extracellular vesicles (EVs) are cell-derived nanovesicles, that not only possess the basic characteristics and functions of their corresponding maternal cells but also contain several outstanding advantages including abundant sources, excellent biocompatibility, and convenient administration routes. Furthermore, the membrane surface and cavity are easy to flexibly modify to meet versatile application needs. Recently, MSC-derived EVs have emerged as promising therapeutics for skin wound repair. However, current reviews are too broad and rarely focused on the specific roles of EVs in the different stages of wound recovery. Therefore, it is quite necessary to demonstrate the significance of stem cell-derived EVs in promoting wound healing from several specific aspects. Here, this review primarily tries to provide critical comments on current advances in EVs derived from MSCs for wound repair, particularly elaborating on their impressive roles in effectively eliminating infections, inhibiting inflammation, promoting angiogenesis, and reducing scar formation. Last but not least, current limitations and future prospects of EVs derived from MSCs in the areas of wound repair are also objectively analyzed.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Cicatriz/metabolismo , Nanomedicina , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo
8.
Toxins (Basel) ; 14(12)2022 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-36548782

RESUMO

Type B trichothecenes commonly contaminate cereal grains and include five structurally related congeners: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), and nivalenol (NIV). These toxins are known to have negative effects on human and animal health, particularly affecting food intake. However, the pathophysiological basis for anorexic effect is not fully clarified. The purpose of this study is to explore the potential roles of the brain-gut peptides substance P (SP) and glucagon-like peptide-17-36 amide (GLP-1) in anorexic responses induced by type B trichothecenes following both intraperitoneal (IP) and oral administration. SP and GLP-1 were elevated at 1 or 2 h and returned to basal levels at 6 h following exposure to DON and both ADONs. FX induced the production of both brain gut peptides with initial time at 1 or 2 h and duration > 6 h. Similar to FX, exposing IP to NIV caused elevations of SP and GLP-1 at 1 h and lasted more than 6 h, whereas oral exposure to NIV only increased both brain gut peptides at 2 h. The neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and DON-induced anorexic responses. Pretreatment with the GLP-1 receptor (GLP-1R) antagonist Exending9-39 induced a dose-dependent attenuation of both GLP-1- and DON-induced anorexic responses. To summarize, the results suggest that both SP and GLP-1 play important roles in anorexia induction by type B trichothecenes.


Assuntos
Depressores do Apetite , Tricotecenos do Tipo B , Tricotecenos , Animais , Humanos , Anorexia/induzido quimicamente , Substância P/toxicidade , Amidas/toxicidade , Peptídeo 1 Semelhante ao Glucagon/toxicidade , Tricotecenos/toxicidade , Depressores do Apetite/toxicidade
9.
Hereditas ; 159(1): 39, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36253874

RESUMO

BACKGROUND: Liver ischemia reperfusion injury (LIRI) is not only a common injury during liver transplantation and major hepatic surgery, but also one of the primary factors that affect the outcome of postoperative diseases. However, there are still no reliable ways to tackle the problem. Our study aimed to find some characteristic genes associated with immune infiltration that affect LIRI, which can provide some insights for future research in the future. Therefore, it is essential for the treatment of LIRI, the elucidation of the mechanisms of LIRI, and exploring the potential biomarkers. Efficient microarray and bioinformatics analyses can promote the understanding of the molecular mechanisms of disease occurrence and development. METHOD: Data from GSE151648 were downloaded from GEO data sets, and we performed a comprehensive analysis of the differential expression, biological functions and interactions of LIRI-associated genes. Then we performed Gene ontology (GO) analysis and Kyotoencydlopedia of genes and genomes (KEGG) enrichment analysis of DEGs. At last, we performed a protein-protein interaction network to screen out hub genes. RESULTS: A total of 161 differentially expressed genes (DEGs) were identified. GO analysis results revealed that the changes in the modules were mostly enriched in the neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil mediated immunity. KEGG enrichment analysis of DEGs demonstrated that LIRI mainly involved the cytokine-cytokine receptor interaction. Our data indicated that macrophages and neutrophils are closely related to LIRI. 9 hub genes were screened out in the protein-protein interaction network. CONCLUSIONS: In summary, our data indicated that neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity and cytokine-cytokine receptor interaction may play a key role in LIRI, HRH1, LRP2, P2RY6, PKD1L1, SLC8A3 and TNFRSF8, which were identified as potential biomarkers in the occurrence and development of LIRI. However, further studies are needed to validate these findings and explore the molecular mechanism of these biomarkers in LIRI.


Assuntos
Redes Reguladoras de Genes , Traumatismo por Reperfusão , Biomarcadores , Citocinas/genética , Perfilação da Expressão Gênica/métodos , Humanos , Fígado , Proteínas de Membrana/genética , Receptores de Citocinas/genética , Traumatismo por Reperfusão/genética
10.
Bioorg Med Chem Lett ; 72: 128873, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35779827

RESUMO

A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC50 = 0.88 ± 0.78 µM), which was better than that of Huperzine-A, and its inhibitory effect on BuChE was weak (IC50 = 10.0 ± 1.30 µM), which indicated that compound 10q was a dominant AChE inhibitor. In addition, the result of molecular docking study displayed that 10q could simultaneously bind to CAS and PAS sites of AChE, which was consistent with the mixed inhibition mode shown by the enzymatic kinetics study of 10q. Furthermore, the molecular properties of the target compounds were predicted online using the molinspiration server and pkCSM, The results exhibited that compound 10q had drug-like properties that satisfied the Lipinski's rule of five. Based on the bioactivity and molecular properties, compound 10q for further development was valuable.


Assuntos
Doença de Alzheimer , Inibidores da Colinesterase , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Pirimidinas/farmacologia , Relação Estrutura-Atividade
11.
Toxins (Basel) ; 14(6)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35737032

RESUMO

Deoxynivalenol (DON), the most naturally-occurring trichothecenes, may affect animal and human health by causing vomiting as a hallmark of food poisoning. Deoxynivalenol-3-glucoside (D3G) usually co-occurs with DON as its glucosylated form and is another emerging food safety issue in recent years. However, the toxicity of D3G is not fully understood compared to DON, especially in emetic potency. The goals of this research were to (1) compare emetic effects to D3G by oral and intraperitoneal (IP) routes and relate emetic effects to brain-gut peptides glucose-dependent insulinotropic polypeptide (GIP) and substance P (SP) in mink; (2) determine the roles of calcium-sensing receptor (CaSR) and transient receptor potential (TRP) channel in D3G's emetic effect. Both oral and IP exposure to D3G elicited marked emetic events. This emetic response corresponded to an elevation of GIP and SP. Blocking the GIP receptor (GIPR) diminished emetic response induction by GIP and D3G. The neurokinin 1 receptor (NK-1R) inhibitor Emend® restrained the induction of emesis by SP and D3G. Importantly, CaSR antagonist NPS-2143 or TRP channel antagonist ruthenium red dose-dependently inhibited both D3G-induced emesis and brain-gut peptides GIP and SP release; cotreatment with both antagonists additively suppressed both emetic and brain-gut peptide responses to D3G. To summarize, our findings demonstrate that activation of CaSR and TRP channels contributes to D3G-induced emesis by mediating brain-gut peptide exocytosis in mink.


Assuntos
Eméticos , Tricotecenos , Animais , Eméticos/toxicidade , Glucose , Glucosídeos , Vison , Receptores Acoplados a Proteínas G , Receptores dos Hormônios Gastrointestinais , Substância P , Tricotecenos/química , Tricotecenos/toxicidade , Vômito/induzido quimicamente
12.
Toxins (Basel) ; 14(6)2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35737050

RESUMO

The T-2 toxin, a major secondary metabolite of Fusarium Gramineae, is considered a great risk to humans and animals due to its toxicity, such as inducing emesis. The mechanism of emesis is a complex signal involving an imbalance of hormones and neurotransmitters, as well as activity of visceral afferent neurons. The T-2 toxin has been proven to induce emesis and possess the capacity to elevate expressions of intestinal hormones glucagon-like peptide-17-36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both of which are important emetic factors. In addition, the activation of calcium-sensitive receptor (CaSR) and transient receptor potential (TRP) channels are engaged in intestinal hormone release. However, it is unknown whether hormones GLP-1 and GIP mediate T-2 toxin-induced emetic response through activating CaSR and TRP channels. To further assess the mechanism of T-2 toxin-induced emesis, we studied the hypothesis that T-2 toxin-caused emetic response and intestinal hormones GLP-1 and GIP released in mink are associated with activating calcium transduction. Following oral gavage and intraperitoneal injection T-2 toxin, emetic responses were observed in a dose-dependent manner, which notably corresponded to the secretion of GLP-1 and GIP, and were suppressed by pretreatment with respective antagonist Exending9-39 and Pro3GIP. Additional research found that NPS-2143 (NPS) and ruthenium red (RR), respective antagonists of CaSR and TRP channels, dramatically inhibited both T-2 toxin-induced emesis response and the expression of plasma GLP-1 and GIP. According to these data, we observed that T-2 toxin-induced emetic response corresponds to secretion of GLP-1 and GIP via calcium transduction.


Assuntos
Toxina T-2 , Amidas , Animais , Cálcio , Eméticos , Polipeptídeo Inibidor Gástrico/metabolismo , Polipeptídeo Inibidor Gástrico/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose/farmacologia , Insulina , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G , Toxina T-2/toxicidade , Vômito
13.
J Tradit Chin Med ; 42(1): 49-57, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35322632

RESUMO

OBJECTIVE: To evaluate the therapeutic effectiveness of salidroside (Sal) and pyrrolidine dithiocarbamate (PDTC) against severe acute pancreatitis (SAP) in a rat model. METHODS: Rat models of SAP were established by retrograde infusion of sodium taurocholate solution. SAP rats were randomly divided into 6 groups: SAP 3 h group, SAP 24 h group, low-dose Sal treatment group (Sal L+S), middle-dose Sal treatment group (Sal M+S), high-dose Sal treatment group (Sal H+S) and PDTC treatment group (PDTC+S). The serum amylase, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-10 (IL-10) levels were determined by optical turbidimetry and enzyme-linked immunosorbent assay. The expression of Beclin-1, microtubule-associated protein light chain 3II (LC3 II ), lysosome associated membrane protein 2 (LAMP2), interleukin-1 receptor associated kinase 1 (IRAK1) inhibitor α of nuclear transcription factor-kB (IkBα), nuclear transcription factor-kB 65 (p65) in the pancreas tissues were detected by quantitative real-time polymerase chain reaction and Western blot, while the pIkBα and p-p65 levels were detected by Western blot. Pathological changes of the pancreas and all the other indexes were observed at 3 and 24 h after operation. RESULTS: The serum IL-10 level, IkBα and LAMP2 levels in Sal M+S, Sal H+S and PDTC+S groups were higher than those in SAP 24 h group, while all the other indexes in these three groups were all lower significantly than those in SAP 24 h group. There was no significant difference in all indexes between Sal H+S and PDTC+S groups. CONCLUSION: High-dose Sal has an effectively therapeutic effect on SAP in rats, which was similar to PDTC.


Assuntos
Pancreatite , Doença Aguda , Animais , Glucosídeos , Humanos , Interleucina-10/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Fenóis , Pirrolidinas , Ratos , Ratos Sprague-Dawley , Tiocarbamatos , Fatores de Transcrição/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
14.
Biomed Res Int ; 2021: 1994764, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595234

RESUMO

Breast cancer is one of the most common malignancies. Pathological image processing of breast has become an important means for early diagnosis of breast cancer. Using medical image processing to assist doctors to detect potential breast cancer as early as possible has always been a hot topic in the field of medical image diagnosis. In this paper, a breast cancer recognition method based on image processing is systematically expounded from four aspects: breast cancer detection, image segmentation, image registration, and image fusion. The achievements and application scope of supervised learning, unsupervised learning, deep learning, CNN, and so on in breast cancer examination are expounded. The prospect of unsupervised learning and transfer learning for breast cancer diagnosis is prospected. Finally, the privacy protection of breast cancer patients is put forward.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Processamento de Imagem Assistida por Computador , Neoplasias da Mama/diagnóstico , Feminino , Humanos
15.
Nat Prod Res ; 35(22): 4442-4447, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32081038

RESUMO

One new long-chain ester derivative of trans-ferulic acid 1 and one natural tirucallane-type triterpenoid 2, together with forty known compounds (3-42), were isolated from the barks of Melia azedarach. Their structures were established on the basis of spectroscopic data interpretation. Compounds 7, 9, 10, 12, 13 showed significant inhibitory activities against PTP1B with IC50 values of 13.82 ± 1.29 µM, 13.29 ± 2.26 µM, 20.27 ± 0.52 µM, 24.36 ± 1.25 µM, 15.23 ± 0.6 µM, respectively.


Assuntos
Melia azedarach , Proteína Tirosina Fosfatase não Receptora Tipo 1
16.
Front Pharmacol ; 11: 546825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041792

RESUMO

OBJECTIVE: The aim of this study was to eluc\idate the preventive and therapeutic effects and the underlying mechanisms of Huoxue Huatan Decoction (HXHT) on myocardial ischemia/reperfusion (I/R) injury in hyperlipidemic rats. METHODS: An I/R model was established in hyperlipidemic Wistar rats. After 4-8 weeks of HXHT treatment, the physical signs of rats were observed. Lipid metabolism, myocardial enzyme spectrum, cardiac function, myocardial histomorphology, and mitochondrial biosynthesis were investigated by a biochemical method, ultrasonography, electron microscopy, pathological examination, real-time PCR, and Western blot. RESULTS: HXHT can affect lipid metabolism at different time points and significantly reduce the levels of cholesterol (CHO), triglyceride (TG), high-density lipid-cholesterol (HDL-C), and low-density lipid-cholesterol (LDL-C) in hyperlipidemic rats (P < 0.05 or P < 0.01); it can significantly reduce the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), reduce the myocardial infarct size and myocardial ischemic area, and improve cardiac function. The results of myocardial histomorphology showed that HXHT could protect myocardial cells, relieve swelling, reduce the number of cardiac lipid droplets, and improve myocardial mitochondrial function. HXHT could significantly increase the levels of total superoxide dismutase (T-SOD) and succinate dehydrogenase (SDH) (P < 0.05 or P < 0.01), increase CuZn-superoxide dismutase (CuZn-SOD) and glutathione-peroxidase (GSH-Px) levels, and decrease the levels of malondialdehyde (MDA) (P < 0.05); it could increase the mRNA and protein expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (mtTFA) (P < 0.05 or P < 0.01), and increase the synthesis of mitochondrial DNA (mtDNA) (P < 0.01). CONCLUSION: HXHT can reduce myocardial I/R injury in hyperlipidemic rats. The protective mechanisms may involve a reduction in blood lipids, enhancement of PGC-1α-PPARα pathway activity, and, subsequently, an increase in fatty acid ß-oxidation, which may provide the required input for mitochondrial energy metabolism. HXHT can additionally enhance PGC-1α-NRF1-mtTFA pathway activity and, subsequently, increase the antioxidant capacity, promote mtDNA synthesis, and reduce mitochondrial damage. The two pathways use PGC-1α as the intersection point to protect mitochondrial structure and function, reduce I/R-induced injury, and improve cardiac function.

17.
Huan Jing Ke Xue ; 41(3): 1045-1055, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608604

RESUMO

To investigate the variations and sources of n-alkanes and sugars in Taian City during summer, PM2.5 samples were collected from July 22 to August 19, 2016. The identified n-alkane and sugar sources were investigated using a principal component analysis (PCA) multiple linear regression (MLR) model and a backward trajectory model. The results showed that the mass concentrations of PM2.5 during summer were (37.2±11.5) µg·m-3. The mass concentrations of n-alkanes were (83.3±34.7) ng·m-3, the carbon preference index (CPI) was 1.83, and the relative contribution of wax n-alkanes was 34.7%-69.4%, suggesting that contributions from terrestrial plants were more significant in Taian City. The results showed that the mass concentrations of sugars in Taian City during summer were (73.4±46.6) ng·m-3. Levoglucan, galactosan, and mannosan were the main saccharides, accounting for 64.0%, 7.1%, and 6.3% of the total concentrations of sugars, respectively, indicating that biomass burning is much more significant in Taian City. The results of the PCA-MLR model suggested that n-alkanes and sugars in Taian City during summer were mostly from terrestrial plants, coal burning and biomass burning. The backward trajectory model showed that the pollution mostly came from the native sources of Shandong province and the inland cities in the south.

18.
Huan Jing Ke Xue ; 40(10): 4319-4329, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854798

RESUMO

To investigate the diurnal variations and sources of water-soluble compounds in Liaocheng City, PM2.5 samples were collected between January and February 2017. The PM2.5 samples were analyzed for the compositions, concentrations, and sources of water-soluble inorganic ions, oxalic acid, and levoglucosan. The sources of these chemical compound were investigated using principal component analysis (PCA) and multiple linear regression (MLR) modeling. The results showed that the mass concentrations of PM2.5during the nighttime were higher than those during the daytime, and the average concentrations exceeded the National Ambient Air Quality Standard (GB 3095-2012) by more than 1.8 times. Moreover, atmospheric pollution was worse during the day than during the night. SNA (SO42-, NO3-, and NH4+) were the dominant species among the inorganic ions, the relative abundance of which with respect to the total concentrations of inorganic ions was 73.4% and 77.1% during the daytime and nighttime, respectively. The ratios of anion to cation equivalents (AE/CE) were less than one, suggesting that the PM2.5 was slightly alkaline, and the degree of acidity at night was stronger than during the day. The results of the correlation analyses suggested that aqueous-phase oxidation was the major formation pathway of oxalic acid, which is driven by acid-catalyzed oxidation. The oxalic acid was mainly influenced by biomass burning during the winter in Liaocheng City. The results of the PCA-MLR model suggested that water-soluble compounds in Liaocheng City were mostly from vehicular emissions and secondary oxidation, biomass burning, while the impacts of mineral dust and coal burning were relatively minor.

19.
Huan Jing Ke Xue ; 40(9): 3875-3885, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854849

RESUMO

To investigate the mass concentrations, sources, and health effects of polycyclic aromatic hydrocarbons (PAHs) in ambient particulate matter (PM) in Liaocheng City during winter, 14 types of PAHs in PM2.5 were determined from January to February of 2017. The sources of the PAHs were analyzed by using diagnostics ratios and the principal component analysis (PCA)-multiple linear regression (MLR) model,and the health risk of PAHs was assessed by BaP equivalent concentrations (BaPeq) and incremental lifetime cancer risk (ILCR). The results showed that the mass concentrations of PAHs in PM2.5 during winter were (64.89±48.23) ng·m-3, Fla, Pyr, and Chry were predominant species, accounting for 15.5%, 12.8%, and 12.7% of the total concentrations of PAHs, respectively. Moreover, the ring distribution of the PAHs was dominated by four-ring PAHs. The pollution during the pre-Spring Festival and firework Ⅱwere the most severe during the sampling period. The results of the PCA-MLR model suggested that PAHs originated mostly from coal burning, biomass burning, and vehicle emissions. The toxicity exposure index (TEQ) in Liaocheng City during winter was (6.37±4.92) ng·m-3. The results of the risk model revealed that the ILCR of adults was higher than that of children, and both groups of ILCR for winter were in the range of the risk threshold. This suggests that a potential risk in terms of inhalation PAH exposure for residents in Liaocheng City.


Assuntos
Poluentes Atmosféricos , Saúde Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Medição de Risco , Adulto , Criança , China , Cidades , Monitoramento Ambiental , Humanos , Material Particulado , Estações do Ano
20.
Huan Jing Ke Xue ; 40(2): 548-557, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628316

RESUMO

To investigate molecular composition, mass concentrations, and sources of n-alkanes and sugars which are adsorbed in ambient particulate matters in Liaocheng City during winter, PM2.5 samples were collected from January 17 to February 15, 2017 at Liaocheng University. 19 kinds (C18-C36) of n-alkanes and 10 kinds of sugars were determined using GC-MS. The identification of n-alkane and sugar sources were investigated using principal component analysis (PCA). The results showed that the mass concentrations of total n-alkanes in PM2.5 during the winter were (456.9±252.5) ng·m-3. During the haze period, the concentrations of n-alkanes were two times higher than those on clear days. Additionally, the concentrations of n-alkanes during fireworks event I and fireworks event Ⅱ were 0.9 times and 1.2 times higher than those on clear days. During the sampling period, the Carbon preference index (CPI) was 1.2±0.1, and the contribution from plant wax concentrations for n-alkanes (% Wax Cn) was between 3.1%~36.0%, indicating that fossil fuels were the major source of n-alkanes in Liaocheng City during the winter. The mass concentrations of saccharides in PM2.5 during the winter were (415.5±213.8) ng·m-3. Levoglucosan was the most abundant species, followed by galactosan and mannosan, which accounted for more than 91.6% of total saccharides, indicating that biomass burning was much more significant in Liaocheng City. PCA further suggested that n-alkane and saccharide compounds in atmospheric aerosol during the winter in Liaocheng City were primarily derived from fossil fuel and biomass burning.

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